Variant chr1-237591888-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001035.3(RYR2):c.4275+35C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,478,018 control chromosomes in the GnomAD database, including 163,182 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 13283 hom., cov: 31)

Exomes 𝑓: 0.47 ( 149899 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.272

Variant links:

Genes affected

RYR2 (HGNC:10484): (ryanodine receptor 2) This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia. [provided by RefSeq, Jul 2008]

RYR2 links:

RYR2 (HGNC:):

RYR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BP6

Variant 1-237591888-C-T is Benign according to our data. Variant chr1-237591888-C-T is described in ClinVar as [Benign]. Clinvar id is 257211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3 linkuse as main transcript	c.4275+35C>T		intron_variant		ENST00000366574.7	NP_001026.2	Q92736-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RYR2	ENST00000366574.7 linkuse as main transcript	c.4275+35C>T	intron_variant	1	NM_001035.3	ENSP00000355533.2	Q92736-1
RYR2	ENST00000609119.2 linkuse as main transcript	n.4275+35C>T	intron_variant	5		ENSP00000499659.2	A0A590UK06
RYR2	ENST00000660292.2 linkuse as main transcript	c.4275+35C>T	intron_variant			ENSP00000499787.2	A0A590UKB7
RYR2	ENST00000659194.3 linkuse as main transcript	c.4275+35C>T	intron_variant			ENSP00000499653.3	A0A590UJZ8

Frequencies

GnomAD3 genomes

AF:

0.395

AC:

59969

AN:

151834

Hom.:

13278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.499

Gnomad ASJ

AF:

0.468

Gnomad EAS

AF:

0.325

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.501

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.482

Gnomad OTH

AF:

0.416

GnomAD3 exomes

AF:

0.454

AC:

92391

AN:

203378

Hom.:

22071

AF XY:

0.449

AC XY:

48820

AN XY:

108704

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.606

Gnomad ASJ exome

AF:

0.474

Gnomad EAS exome

AF:

0.313

Gnomad SAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.510

Gnomad NFE exome

AF:

0.482

Gnomad OTH exome

AF:

0.476

GnomAD4 exome

AF:

0.470

AC:

623619

AN:

1326066

Hom.:

149899

Cov.:

AF XY:

0.467

AC XY:

308904

AN XY:

661788

show subpopulations

Gnomad4 AFR exome

AF:

0.178

Gnomad4 AMR exome

AF:

0.597

Gnomad4 ASJ exome

AF:

0.475

Gnomad4 EAS exome

AF:

0.353

Gnomad4 SAS exome

AF:

0.337

Gnomad4 FIN exome

AF:

0.505

Gnomad4 NFE exome

AF:

0.489

Gnomad4 OTH exome

AF:

0.445

GnomAD4 genome

AF:

0.395

AC:

59975

AN:

151952

Hom.:

13283

Cov.:

AF XY:

0.396

AC XY:

29435

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.500

Gnomad4 ASJ

AF:

0.468

Gnomad4 EAS

AF:

0.325

Gnomad4 SAS

AF:

0.324

Gnomad4 FIN

AF:

0.501

Gnomad4 NFE

AF:

0.482

Gnomad4 OTH

AF:

0.411

Alfa

AF:

0.442

Hom.:

4149

Bravo

AF:

0.391

Asia WGS

AF:

0.314

AC:

1092

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 15, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.21

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over